Localized Wegener's granulomatosis: Predominance of CD26 and IFN-gamma expression

The immune response in Wegener's granulomatosis (WG) has been characterized as predominant, potentially pathogenic Th1-like reaction by blood T cells and T-cell clones from diseased tissues. To elucidate further the immunopat hogenic mechanisms, this study analysed the phenotypes of inflammatory infi ltrates in frozen nasal biopsies with involvement of the upper respiratory tract only (localized or 'initial phase' WG) and with multi-organ involveme nt, including systemic vasculitis (generalized WG). The expression and prod uction of Th1 and Th2 cytokines were examined in tissue specimens and perip heral blood mononuclear cells (PBMCs) of localized and generalized WG. The number of CD3 + T cells in inflammatory infiltrates ranged from 50 to 70%, together with approximately 30% CD14+ monocytes/macrophages. An average of 40% of T cells expressed CD26 in nasal biopsies of localized WG, compared w ith about 16% in specimens of generalized WG, in parallel, a higher number of interferon-gamma (IFN-gamma)-positive cells were detected in nasal tissu e of localized than in generalized WC. PBMCs from localized WG similarly ex hibited higher spontaneous IFN-gamma production in contrast to generalized WG (207 vs. 3 pg/ml, p < 0.05). Interleukin-4 (IL-4) mRNA was found in high er amounts in generalized than in localized WG, IL-4 production was negligi ble in both disease and controls. In addition, both IL-10 mRNA and IL-10 pr otein levels of activated PBMCs from localized WG were elevated when compar ed,with generalized disease (574 vs. 154 pg/ml, p < 0.05) or healthy contro ls (574 vs. 246 pg/ml, p < 0.05). It is conluded that in nasal tissues, mai nly CD4 +/ CD26 + T cells as well as IFN-gamma-positive cells may support a polarized Th1-like immune response. Furthermore, the data suggest that thi s in situ immune response is already initiated and established in localized WG, accompanied by increased peripheral IFN-gamma and IL-10 production. Co pyright (C) 2000 John Wiley & Sons, Ltd.